Dimethylformamide → HCID 22082693, compound

HRID 1827677Notes

Reaction equation

HRID 1827677 reaction equation
Cl[C:2]1[C:11]([CH:12]2[CH2:14][CH2:13]2)=[CH:10][C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.CCN([CH2:20][CH3:21])CC.CN(C=[O:26])C.[CH2:27]1[CH2:31][O:30][CH2:29][CH2:28]1>CCO.[Cu]I.O=[Pt]=O>[CH3:31][O:30][C:29](=[O:26])[CH2:28][CH2:27][CH2:20][CH2:21][C:2]1[C:11]([CH:12]2[CH2:14][CH2:13]2)=[CH:10][C:9]2[CH2:8][CH2:7][CH2:6][NH:5][C:4]=2[N:3]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8028TetrahydrofuranHCID 8471Triethylamine2×HCID 22062921HCID 22062921, compound

Product 1

HCID 22082693HCID 22082693, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 345198Adams' catalystCatalystHCID 702EthanolSolvent

Conditions

Temperature
53 °C

Procedure

A mixture of naphthyridine 2-5 (15.8 g, 77.2 mmol), ester 2-6 (prepared from 4-pentynoic acid and methanolic HCl solution, 11.3 g, 100.4 mmol), CuI (0.7 g, 3.9 mmol), 100 mL Et3N and 100 mL DMF was gently degassed with argon for 10 min. Then Pd(PPh3)2Cl2 was added in one portion. The reaction mixture was heated at 53° C. for 20 hr, cooled to room temperature and quenched with 500 mL water and 100 mL NaHCO3 (sat.). The aqueous mixture was extracted three times with ethyl acetate. The combined organic layer was washed with brine and dried over MgSO4. After solvent removal, the residue was purified by silica gel flash chromatography (EtOAc/Hexane=¼ to 100% EtOAc over 30 min) to afford an oil, which was subsequently dissolved in 150 mL THF and 50 mL EtOH. Et3N (15 mL, 104 mmol) and PtO2 (0.7 g) were added. The mixture was degassed under moderate vacuum and subjected to balloon hydrogenation condition for 6 hrs. It was then filtered and concentrated to provide the desired product 2-7 as an oil.

Workup

  1. customwas gently degassed with argon for 10 min
  2. additionThen Pd(PPh3)2Cl2 was added in one portion
  3. temperaturecooled to room temperature
  4. customquenched with 500 mL water and 100 mL NaHCO3 (sat.)
  5. extractionThe aqueous mixture was extracted three times with ethyl acetate
  6. washThe combined organic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. customAfter solvent removal
  9. customthe residue was purified by silica gel flash chromatography (EtOAc/Hexane=¼ to 100% EtOAc over 30 min)
  10. customto afford an oil, which
  11. customThe mixture was degassed under moderate vacuum
  12. customfor 6 hrs
  13. filtrationIt was then filtered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-c107420f56964a98a3bca82940b14ebb
Source dataset
uspto-grants-2006_06
Patent number
US07056909B2

Reaction notes

Loading…